We have recently observed that lymphocytes of patients with lymphoma and lymphocytes of normal cancer hospital workers, but not those of normal non-hospital employees or patients with other types of neoplasias, inhibit colony formation by an established human lymphoma cell line. This is one of the first such demonstrations of which we are aware. Therefore, we propose to further develop a variety of immunodiagnostic assays utilizing this long-term culture of lymphoma cells now known to synthesize a cross-reacting tumor-associated antigen(s) and to use such assays to investigate the presence and mechanisms of antilymphoma immune responses. Cytotoxic effects will be studied by the Cr51 release and colony-formation inhibition techniques by cocultivating target cells and purified peripheral blood lymphocytes, macrophages or their combination. Detection and titration of specific antilymphoma antibodies will be carried out by immunofluorescence and immunoperoxidase methods. Antibody class will be defined by the use of monospecific antisera and affinity chromatography. Antibody blocking effects will be defined by preincubation of target cells with autologous and appropriate allogeneic sera. Antibody-dependent cell-mediated cytotoxicity will be determined by incubating target cells with sera followed by cocultivation with normal lymphocytes. Antibody-mediated immunostimulatory effects will be determined by investigating proliferation kinetics while the target cells are under the influence of the specific antitumor antibody. Serial studies will be done on lymphoma, leukemia, and other cancer patients, family members, normal hospital employees and other normal subjects. The objective will be to determine the exact spectrum of reactivity, the relationship between humoral and cell-mediated immunity, the mechanism of the colony- inhibition and the time and incidence of development of reactivity after exposure to lymphoma patients.